tbuckley/cabot-search huggingface dataset:
Identification of Subclinical Heart Failure With Preserved Ejection Fraction in Patients With Symptomatic Atrial Fibrillation
Authors: Jonathan P. Ariyaratnam, Adrian D. Elliott, Ricardo S. Mishima, Kadhim Kadhim, Olivia McNamee, Pawel Kuklik, Mehrdad Emami, Varun Malik, John L. Fitzgerald, Celine Gallagher, Dennis H. Lau, Prashanthan Sanders
Journal: JACC Heart Failure (2023)
Cardiac Amyloid Quantification Using 124I-Evuzamitide (124I-P5+14) Versus 18F-Florbetapir
Authors: Olivier F. Clerc, Sarah A.M. Cuddy, Matthew Robertson, Shilpa Vijayakumar, Jocelyn Canseco Neri, Vaidehi Chemburkar, Marie Foley Kijewski, Marcelo F. Di Carli, Giada Bianchi, Rodney H. Falk, Sharmila Dorbala
Journal: JACC. Cardiovascular imaging (2023)
Assessing Donor-Recipient Size Mismatch in Pediatric Heart Transplantation
Authors: Shahnawaz Amdani, Othman A. Aljohani, James K. Kirklin, Ryan Cantor, Devin Koehl, Kurt Schumacher, Deipanjan Nandi, Michael Khoury, William Dreyer, Kirsten Rose-Felker, Colleen Nasman, Mariska S. Kemna
Journal: JACC Heart Failure (2023)
Short-Term Changes in Peak VO2 After Initiation of Dapagliflozin in Heart Failure Across Iron Status
Authors: Miguel Lorenzo, Conxita Jacobs-Cachá, Patricia Palau, Martina Amiguet, Julia Seller, Eduardo Núñez, Rafael de la Espriella, Jose Luis Górriz, Gema Miñana, Juan Sanchis, Antoni Bayés-Genis, Maria José Soler, Milton Packer, Julio Núñez, Patricia Palau, Martina Amiguet, Eloy Domínguez, Clara Sastre, Anna Mollar, Julia Seller, Jose Manuel Garcia Pinilla, Ainoha Larumbe, Alfonso Valle, Juan Jose Gómez Doblas, Rafael de la Espriella, Gema Miñana, Sandra Villar, Ainhoa Robles Mezcua, Enrique Santas, Vicent Bodí, Juan Sanchis, Domingo Pascual-Figal, Jose Luis Górriz, Antonio Baýes-Genís, Jose Civera, Adriana Conesa, Rim Zakarne, Clara Jiménez Rubio, Alejandro I. Pérez Cabeza, Arancha Díaz Expósito, José David Martínez Carmona, Manuel Luna Morales, Francisco J. Zafra Sánchez, Ángel Montiel Trujillo, Herminio Morillas Climent, Julio Núñez
Journal: JACC Heart Failure (2023)
Mechanical Wave Velocities in Left Ventricular Walls in Healthy Subjects and Patients With Aortic Stenosis
Authors: Torvald Espeland, Morten S. Wigen, Havard Dalen, Erik A.R. Berg, Tommy A. Hammer, Sebastien Salles, Lasse Lovstakken, Brage H. Amundsen, Svend Aakhus
Journal: JACC. Cardiovascular imaging (2023)
Intrarenal Venous Flow Pattern Changes Do Relate With Renal Function Alterations in Acute Heart Failure
Authors: Rafael de la Espriella, Gonzalo Núñez-Marín, Marta Cobo, Daniel de Castro Campos, Pau Llácer, Luis Manzano, Isabel Zegrí, Álvaro Rodriguez-Pérez, Enrique Santas, Miguel Lorenzo, Gema Miñana, Eduardo Núñez, Jose Luis Górriz, Antoni Bayés-Genís, Marat Fudim, Wilfried Mullens, Julio Núñez
Journal: JACC Heart Failure (2023)
A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of Alzheimer’s disease
Authors: Rafi Haque, Caroline M. Watson, Jiaqi Liu, E. Kathleen Carter, Duc M. Duong, James J. Lah, Aliza P. Wingo, Blaine R. Roberts, Erik C. B. Johnson, Andrew J. Saykin, Leslie M. Shaw, Nicholas T. Seyfried, Thomas S. Wingo, Allan I. Levey
Journal: Science Translational Medicine (2023)

Alzheimer’s disease (AD) is a neurodegenerative disease with heterogenous pathophysiological changes that develop years before the onset of clinical symptoms. These preclinical changes have generated considerable interest in identifying markers for the pathophysiological mechanisms linked to AD and AD-related disorders (ADRD). On the basis of our prior work integrating cerebrospinal fluid (CSF) and brain proteome networks, we developed a reliable and high-throughput mass spectrometry–selected reaction monitoring assay that targets 48 key proteins altered in CSF. To test the diagnostic utility of these proteins and compare them with existing AD biomarkers, CSF collected at baseline visits was assayed from 706 participants recruited from the Alzheimer’s Disease Neuroimaging Initiative. We found that the targeted CSF panel of 48 proteins (CSF 48 panel) performed at least as well as existing AD CSF biomarkers (Aβ 42 , tTau, and pTau 181 ) for predicting clinical diagnosis, FDG PET, hippocampal volume, and measures of cognitive and dementia severity. In addition, for each of those outcomes, the CSF 48 panel plus the existing AD CSF biomarkers significantly improved diagnostic performance. Furthermore, the CSF 48 panel plus existing AD CSF biomarkers significantly improved predictions for changes in FDG PET, hippocampal volume, and measures of cognitive decline and dementia severity compared with either measure alone. A potential reason for these improvements is that the CSF 48 panel reflects a range of altered biology observed in AD/ADRD. In conclusion, we show that the CSF 48 panel complements existing AD CSF biomarkers to improve diagnosis and predict future cognitive decline and dementia severity.
Relationship of Daily Step Counts to All-Cause Mortality and Cardiovascular Events
Authors: Niels A. Stens, Esmée A. Bakker, Asier Mañas, Laurien M. Buffart, Francisco B. Ortega, Duck-chul Lee, Paul D. Thompson, Dick H.J. Thijssen, Thijs M.H. Eijsvogels
Journal: Journal of the American College of Cardiology (2023)
Cost-effectiveness analysis of interventions to improve diagnosis and preventive therapy for paediatric tuberculosis in 9 sub-Saharan African countries: A modelling study
Authors: Nyashadzaishe Mafirakureva, Sushant Mukherjee, Mikhael de Souza, Cassandra Kelly-Cirino, Mario J. P. Songane, Jennifer Cohn, Jean-François Lemaire, Martina Casenghi, Peter J. Dodd
Journal: PLoS Medicine (2023)

Over 1 million children aged 0 to 14 years were estimated to develop tuberculosis in 2021, resulting in over 200,000 deaths. Practical interventions are urgently needed to improve diagnosis and antituberculosis treatment (ATT) initiation in children aged 0 to 14 years and to increase coverage of tuberculosis preventive therapy (TPT) in children at high risk of developing tuberculosis disease. The multicountry CaP-TB intervention scaled up facility-based intensified case finding and strengthened household contact management and TPT provision at HIV clinics. To add to the limited health-economic evidence on interventions to improve ATT and TPT in children, we evaluated the cost-effectiveness of the CaP-TB intervention.We analysed clinic-level pre/post data to quantify the impact of the CaP-TB intervention on ATT and TPT initiation across 9 sub-Saharan African countries. Data on tuberculosis diagnosis and ATT/TPT initiation counts with corresponding follow-up time were available for 146 sites across the 9 countries prior to and post project implementation, stratified by 0 to 4 and 5 to 14 year age-groups. Preintervention data were retrospectively collected from facility registers for a 12-month period, and intervention data were prospectively collected from December 2018 to June 2021 using project-specific forms. Bayesian generalised linear mixed-effects models were used to estimate country-level rate ratios for tuberculosis diagnosis and ATT/TPT initiation. We analysed project expenditure and cascade data to determine unit costs of intervention components and used mathematical modelling to project health impact, health system costs, and cost-effectiveness. Overall, ATT and TPT initiation increased, with country-level incidence rate ratios varying between 0.8 (95% uncertainty interval [UI], 0.7 to 1.0) and 2.9 (95% UI, 2.3 to 3.6) for ATT and between 1.6 (95% UI, 1.5 to 1.8) and 9.8 (95% UI, 8.1 to 11.8) for TPT. We projected that for every 100 children starting either ATT or TPT at baseline, the intervention package translated to between 1 (95% UI, -1 to 3) and 38 (95% UI, 24 to 58) deaths averted, with a median incremental cost-effectiveness ratio (ICER) of US$634 per disability-adjusted life year (DALY) averted. ICERs ranged between US$135/DALY averted in Democratic of the Congo and US$6,804/DALY averted in Cameroon. The main limitation of our study is that the impact is based on pre/post comparisons, which could be confounded.In most countries, the CaP-TB intervention package improved tuberculosis treatment and prevention services for children aged under 15 years, but large variation in estimated impact and ICERs highlights the importance of local context.This evaluation is part of the TIPPI study, registered with ClinicalTrials.gov (NCT03948698).
Intratumoral drug-releasing microdevices allow in situ high-throughput pharmaco phenotyping in patients with gliomas
Authors: Pierpaolo Peruzzi, Christine Dominas, Geoffrey Fell, Joshua D. Bernstock, Sarah Blitz, Debora Mazzetti, Mykola Zdioruk, Hassan Y. Dawood, Daniel V. Triggs, Sebastian W. Ahn, Sharath K. Bhagavatula, Shawn M. Davidson, Zuzana Tatarova, Michael Pannell, Kyla Truman, Anna Ball, Maxwell P. Gold, Veronika Pister, Ernest Fraenkel, E. Antonio Chiocca, Keith L. Ligon, Patrick Y. Wen, Oliver Jonas
Journal: Science Translational Medicine (2023)

The lack of reliable predictive biomarkers to guide effective therapy is a major obstacle to the advancement of therapy for high-grade gliomas, particularly glioblastoma (GBM), one of the few cancers whose prognosis has not improved over the past several decades. With this pilot clinical trial (number NCT04135807), we provide first-in-human evidence that drug-releasing intratumoral microdevices (IMDs) can be safely and effectively used to obtain patient-specific, high-throughput molecular and histopathological drug response profiling. These data can complement other strategies to inform the selection of drugs based on their observed antitumor effect in situ. IMDs are integrated into surgical practice during tumor resection and remain in situ only for the duration of the otherwise standard operation (2 to 3 hours). None of the six enrolled patients experienced adverse events related to the IMD, and the exposed tissue was usable for downstream analysis for 11 out of 12 retrieved specimens. Analysis of the specimens provided preliminary evidence of the robustness of the readout, compatibility with a wide array of techniques for molecular tissue interrogation, and promising similarities with the available observed clinical-radiological responses to temozolomide. From an investigational aspect, the amount of information obtained with IMDs allows characterization of tissue effects of any drugs of interest, within the physiological context of the intact tumor, and without affecting the standard surgical workflow.
Stem-like CD4 <sup>+</sup> T cells in perivascular tertiary lymphoid structures sustain autoimmune vasculitis
Authors: Yuki Sato, Abhinav Jain, Shozo Ohtsuki, Hirohisa Okuyama, Ines Sturmlechner, Yoshinori Takashima, Kevin-Phu C. Le, Melanie C. Bois, Gerald J. Berry, Kenneth J. Warrington, Jörg J. Goronzy, Cornelia M. Weyand
Journal: Science Translational Medicine (2023)

Autoimmune vasculitis of the medium and large elastic arteries can cause blindness, stroke, aortic arch syndrome, and aortic aneurysm. The disease is often refractory to immunosuppressive therapy and progresses over decades as smoldering aortitis. How the granulomatous infiltrates in the vessel wall are maintained and how tissue-infiltrating T cells and macrophages are replenished are unknown. Single-cell and whole-tissue transcriptomic studies of immune cell populations in vasculitic arteries identified a CD4 + T cell population with stem cell–like features. CD4 + T cells supplying the tissue-infiltrating and tissue-damaging effector T cells survived in tertiary lymphoid structures around adventitial vasa vasora, expressed the transcription factor T cell factor 1 (TCF1), had high proliferative potential, and gave rise to two effector populations, Eomesodermin (EOMES) + cytotoxic T cells and B cell lymphoma 6 (BCL6) + T follicular helper-like cells. TCF1 hi CD4 + T cells expressing the interleukin 7 receptor (IL-7R) sustained vasculitis in serial transplantation experiments. Thus, TCF1 hi CD4 + T cells function as disease stem cells and promote chronicity and autonomy of autoimmune tissue inflammation. Remission-inducing therapies will require targeting stem-like CD4 + T cells instead of only effector T cells.
Calprotectin is a contributor to and potential therapeutic target for vascular calcification in chronic kidney disease
Authors: Ana Amaya-Garrido, Manon Brunet, Bénédicte Buffin-Meyer, Alexis Piedrafita, Lucile Grzesiak, Ezechiel Agbegbo, Arnaud Del Bello, Inés Ferrandiz, Serban Ardeleanu, Marcelino Bermudez-Lopez, Camille Fedou, Mylène Camus, Odile Burlet-Schiltz, Jean Massines, Marie Buléon, Guylène Feuillet, Melinda Alves, Eric Neau, Audrey Casemayou, Benjamin Breuil, Jean-Sébastien Saulnier-Blache, Colette Denis, Jakob Voelkl, Griet Glorieux, Sam Hobson, Samsul Arefin, Awahan Rahman, Karolina Kublickiene, Peter Stenvinkel, Jean-Loup Bascands, Stanislas Faguer, José M. Valdivielso, Joost P. Schanstra, Julie Klein
Journal: Science Translational Medicine (2023)

Vascular calcification is an important risk factor for cardiovascular (CV) mortality in patients with chronic kidney disease (CKD). It is also a complex process involving osteochondrogenic differentiation of vascular smooth muscle cells (VSMCs) and abnormal deposition of minerals in the vascular wall. In an observational, multicenter European study, including 112 patients with CKD from Spain and 171 patients on dialysis from France, we used serum proteome analysis and further validation by ELISA to identify calprotectin, a circulating damage-associated molecular pattern protein, as being independently associated with CV outcome and mortality. This was confirmed in an additional cohort of 170 patients with CKD from Sweden, where increased serum calprotectin concentrations correlated with increased vascular calcification. In primary human VSMCs and mouse aortic rings, calprotectin exacerbated calcification. Treatment with paquinimod, a calprotectin inhibitor, as well as pharmacological inhibition of the receptor for advanced glycation end products and Toll-like receptor 4 inhibited the procalcifying effect of calprotectin. Paquinimod also ameliorated calcification induced by the sera of uremic patients in primary human VSMCs. Treatment with paquinimod prevented vascular calcification in mice with chronic renal failure induced by subtotal nephrectomy and in aged apolipoprotein E–deficient mice as well. These observations identified calprotectin as a key contributor of vascular calcification, and increased circulating calprotectin was strongly and independently associated with calcification, CV outcome, and mortality in patients with CKD. Inhibition of calprotectin might therefore be a promising strategy to prevent vascular calcification in patients with CKD.
Podocyte Injury in Diabetic Kidney Disease in Mouse Models Involves TRPC6-mediated Calpain Activation Impairing Autophagy
Authors: Yann Salemkour, Dilemin Yildiz, Léa Dionet, Daan C. ‘t Hart, Kim A.T. Verheijden, Ryuta Saito, Nassim Mahtal, Jean-Daniel Delbet, Emmanuel Letavernier, Marion Rabant, Alexandre Karras, Johan van der Vlag, Tom Nijenhuis, Pierre-Louis Tharaux, Olivia Lenoir
Journal: Journal of the American Society of Nephrology (2023)

Autophagy protects podocytes from injury in diabetic kidney disease (DKD). Restoring glomerular autophagy is a promising approach to limit DKD. This study demonstrates a novel regulatory mechanism of autophagy that blocks this critical protection of the glomerular filtration barrier. We demonstrated that TRPC6 induced in podocytes in mouse models of diabetes mediates calpain activation, thereby impairing podocyte autophagy, causing injury and accelerating DKD. Furthermore, this study provides proof of principle for druggable targets for DKD because restoration of podocyte autophagy by calpain inhibitors effectively limits glomerular destruction.
Humoral immunity to an endemic coronavirus is associated with postacute sequelae of COVID-19 in individuals with rheumatic diseases
Authors: Jonathan D. Herman, Caroline Atyeo, Yonatan Zur, Claire E. Cook, Naomi J. Patel, Kathleen M. Vanni, Emily N. Kowalski, Grace Qian, Shruthi Srivatsan, Nancy A. Shadick, Deepak A. Rao, Benjamin Kellman, Colin J. Mann, Douglas Lauffenburger, Zachary S. Wallace, Jeffrey A. Sparks, Galit Alter
Journal: Science Translational Medicine (2023)

Beyond the acute illness caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) infection, about one-fifth of infections result in long-term persistence of symptoms despite the apparent clearance of infection. Insights into the mechanisms that underlie postacute sequelae of COVID-19 (PASC) will be critical for the prevention and clinical management of long-term complications of COVID-19. Several hypotheses have been proposed that may account for the development of PASC, including persistence of virus and dysregulation of immune responses. Among the immunological changes noted in PASC, alterations in humoral immunity have been observed in some patient subsets. To begin to determine whether SARS-CoV-2– or other pathogen-specific humoral immune responses evolve uniquely in PASC, we performed comprehensive antibody profiling against SARS-CoV-2, a panel of endemic pathogens, and a panel of routine vaccine antigens using systems serology in two cohorts of patients with preexisting systemic autoimmune rheumatic disease (SARD) who either developed or did not develop PASC. A distinct qualitative shift observed in Fcγ receptor (FcγR) binding was observed in individuals with PASC. Specifically, individuals with PASC harbored weaker FcγR-binding anti–SARS-CoV-2 antibodies and stronger FcγR-binding antibody responses against the endemic coronavirus OC43. Individuals with PASC developed an OC43 S2-specific antibody response with stronger FcγR binding, linked to cross-reactivity across SARS-CoV-2 and common coronaviruses. These findings identify previous coronavirus imprinting as a potential marker for the development of PASC in individuals with SARDs.
Treatment and Survival Among Patients With Colorectal Cancer in Sub-Saharan Africa: A Multicentric Population-Based Follow-Up Study
Authors: Lucia Hämmerl, Nikolaus C.S. Mezger, Tobias P. Seraphin, Walburga Yvonne Joko-Fru, Mirko Griesel, Jana Feuchtner, Franck Gnahatin, Freddy Houéhanou Rodrigue Gnangnon, Nathan Okerosi, Phoebe Mary Amulen, Rolf Hansen, Margaret Ziona Borok, Carla Carrilho, Brahima Mallé, Clausina Ahoui Apendi, Nathan G. Buziba, Edom Seife, Biying Liu, Rafael Mikolajczyk, Donald M. Parkin, Eva J. Kantelhardt, Ahmedin Jemal
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: The burden of colorectal cancer (CRC) is increasing in Sub-Saharan Africa (SSA). However, little is known about CRC treatment and survival in the region. Methods: A random sample of 653 patients with CRC diagnosed from 2011 to 2015 was obtained from 11 population-based cancer registries in SSA. Information on clinical characteristics, treatment, and/or vital status was obtained from medical records in treating hospitals for 356 (54%) of the patients (“traced cohort”). Concordance of CRC treatment with NCCN Harmonized Guidelines for SSA was assessed. A Cox proportional hazards model was used to examine the association between survival and human development index (HDI). Results: Of the 356 traced patients with CRC, 51.7% were male, 52.8% were from countries with a low HDI, 55.1% had colon cancer, and 73.6% were diagnosed with nonmetastatic (M0) disease. Among the patients with M0 disease, however, only 3.1% received guideline-concordant treatment, 20.6% received treatment with minor deviations, 31.7% received treatment with major deviations, and 35.1% received no treatment. The risk of death in patients who received no cancer-directed therapy was 3.49 (95% CI, 1.83–6.66) times higher than in patients who received standard treatment or treatment with minor deviations. Similarly, the risk of death in patients from countries with a low HDI was 1.67 (95% CI, 1.07–2.62) times higher than in those from countries with a medium HDI. Overall survival at 1 and 3 years was 70.9% (95% CI, 65.5%–76.3%) and 45.3% (95% CI, 38.9%–51.7%), respectively. Conclusions: Fewer than 1 in 20 patients diagnosed with potentially curable CRC received standard of care in SSA, reinforcing the need to improve healthcare infrastructure, including the oncology and surgical workforce.
Biomarker Testing, Treatment, and Outcomes in Patients With Advanced/Metastatic Non–Small Cell Lung Cancer Using a Real-World Database
Authors: Naleen Raj Bhandari, Lisa M. Hess, Dan He, Patrick Peterson
Journal: Journal of the National Comprehensive Cancer Network (2023)

Background: Little is known about the impact of up-front biomarker testing on long-term outcomes in patients with advanced or metastatic non–small cell lung cancer (a/mNSCLC). This study compared overall survival (OS) by biomarker testing status and by receipt of guideline-concordant therapy in a large real-world cohort of patients with a/mNSCLC in the United States. Patients and Methods: This retrospective study used an a/mNSCLC database derived from real-world electronic healthcare records. Patients diagnosed with nonsquamous a/mNSCLC who initiated first-line therapy on or after January 1, 2015, were included. We describe the testing of patients for actionable biomarkers and whether they subsequently received guideline-recommended first-line treatment. OS was defined as the number of months from the initiation of first-line therapy to the date of death or end of follow-up, and was described using Kaplan-Meier analysis. Multivariable Cox proportional hazard modeling was conducted to compare OS between groups adjusting for baseline covariates; adjusted hazard ratios (HRs) were reported. Results: A total of 21,572 patients with a median age of 69 years (IQR, 61–76 years) and follow-up of 9.5 months (IQR, 3.5–21.5 months) were included. Among patients in the database, 88% had a record of receiving testing for at least 1 biomarker at any time, and 69% of these patients received testing before or at the start of first-line treatment. The adjusted hazard of death was 30% higher in patients who never (vs ever) received biomarker testing in the database (HR, 1.30; 95% CI, 1.24–1.37), and 12% higher in patients who did not receive (vs did receive) biomarker testing before or at the start of first-line treatment (HR, 1.12; 95% CI, 1.08–1.16). The adjusted hazard of death was 25% higher in patients who did not receive guideline-concordant first-line treatment (vs those who did) after having a biomarker-positive disease (HR, 1.25; 95% CI, 1.13–1.40). Conclusions: Findings suggest that receipt of first-line treatment that is concordant with biomarker testing results and treatment guidelines is associated with improved survival outcomes in patients with a/mNSCLC in the United States.